Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-four evaluable patients were treated with vinorelbine, a novel, semisynthetic vinca alkaloid, as first-line chemotherapy for advanced breast cancer. They received vinorelbine 25 mg m-2 i.v. given weekly for a maximum of 16 cycles. Two patients achieved a complete remission and 15 a partial remission, giving a response rate of 17/34 (50%; 95% CI of 34-66%); median response duration was 5.8 months. The median progression-free interval was 4.4 months and median survival 9.9 months. Treatment was generally well tolerated. Fatigue was the most common side-effect. The main reason for dose adjustments was myelosuppression; 68% of patients had WHO grade 3 or 4 neutropenia and there was one death attributed to neutropenic sepsis. Nausea/vomiting and neuropathy were mild and alopecia was uncommon. This study confirms vinorelbine as a highly active, well-tolerated agent in advanced breast cancer worthy of evaluation in combination chemotherapy regimens.
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PMID:A phase II, multicentre, UK study of vinorelbine in advanced breast cancer. 794 9

We conducted a multi-institutional (33 institutes), late phase II study with a 21-consecutive-day oral administration of etoposide for malignant lymphoma. Patient entry criteria were either those refractory to standard therapies or those for whom no appropriate therapy was available. A once-daily dose of 50 mg/body was administered for 21 consecutive days. Of the evaluable 83 among 88 entry patients, the overall response rate was 53.0% (44/83), including 10 CR; 52.5% (42/80, 9 CR) with non-Hodgkin's lymphoma and 100% (2/2, 1 CR) with Hodgkin's disease. Regarding abnormal laboratory findings, myelosuppression was observed; the incidence rates of leukopenia (23.3% with Grade 3), neutropenia (32.6%), hemoglobin decrease (17.4%) and thrombocytopenia (4.7%) were 70.9%, 65.1%, 54.7% and 19.8%, respectively. Major adverse reactions and their incidence were: anorexia 43.0%, alopecia 37.2%, nausea/vomiting 32.6%, fatigue 18.6%, stomatitis 15.1%, fever 7.0% and diarrhea 5.8%. Therefore, a 21-consecutive-day oral administration of 50 mg/body/day or 75 mg/body/day appears to be effective for the treatment of malignant lymphoma.
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PMID:[Late phase II study with 21-consecutive-day oral administration of etoposide for malignant lymphoma]. 799 16

A 30-year-old female was admitted to our hospital complaining of high fever and fatigue. Laboratory findings showed as follows; WBC 41,500/microliter (40% of blasts), Hb 8.5g/dl, platelets 4.4 x 10(4)/microliter. Cytochemical staining of blasts was positive for peroxidase and non-specific esterase with NaF inhibition. Chromosome analysis showed 46, XX, inv (16p+,q-). AML with eosinophilia was diagnosed. During myelosuppression after remission induction therapy, she developed high fever, and did not respond to transfusions. Marrow smears showed the presence of phagocytic histiocytes consisting of 18% total nuclear cells. A diagnosis of reactive histiocytosis (RH) was made. She recovered spontaneously, but suffered two episode of recurrence during subsequent chemotherapy. Reactive histiocytosis is characterized by proliferation of histiocytes which phagocyte blood cells in immunodeficient cases, e.g. a myelosuppressive state after chemotherapy. RH causes high fever and prolonged myelosuppression. It is considered to be one of the poor prognostic factors in AML during chemotherapy, and spontaneous recovery is rare. In this report, the effect of hydrocortisone on histiocytes derived from patient marrow was also investigated in vitro.
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PMID:[A case with AML (M4EO) accompanied by recurrent reactive histiocytosis which showed spontaneous remission]. 802 88

A Phase II trial of combination therapy with recombinant leukocyte interferon (alpha IFN) and doxorubicin was performed in patients with unresectable hepatocellular carcinoma. alpha IFN was administered at a starting dose of 20 x 10(6) U/m2 intramuscularly or subcutaneously with doxorubicin 20 mg/m2 intravenously weekly x 3 weeks followed by a 2-week period rest. There were 22 patients entered into the study. Among the 21 patients, there were 2 partial responses (10%), one minor response, and one patient had stable disease. Toxicity was generally tolerable, with fever, fatigue, and myelosuppression being the most common side effects. This combination of weekly recombinant leukocytic interferon and doxorubicin has modest and limited activity in hepatocellular carcinoma.
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PMID:A phase II trial of recombinant leukocyte interferon plus doxorubicin in patients with hepatocellular carcinoma. 809 9

During a phase I clinical and pharmacologic trial, 26 patients with refractory solid tumors were treated with increasing doses of adozelesin by brief intravenous infusion every 3 weeks. Overall, adozelesin was well tolerated. The dose-limiting toxicity was myelosuppression, mainly thrombocytopenia and leukopenia. Nonhematologic toxicity was generally mild, with fatigue (36%), local reaction at the infusion site (24%), nausea or vomiting (20%) and hypersensitivity reaction (16%) being the most common adverse effects. There were no objective clinical responses. The maximally tolerated dose on this schedule was 188 micrograms/m2 with the recommended phase II starting dose being 150 micrograms/m2 on an every 3 week schedule. Adozelesin merits broad investigation at the phase II level.
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PMID:Phase I study of adozelesin (U-73,975) in patients with solid tumors. 818 23

A total of 21 patients with advanced cancer were entered into a phase I study to determine the maximum tolerable dose (MTD) of liposome-encapsulated doxorubicin (LED) given weekly for 3 consecutive weeks at doses of 20, 30, or 37.5 mg/m2 per week. For a comparison of the pharmacokinetic behavior of LED with that of standard-formulation doxorubicin, 13 patients received a dose of standard-formulation doxorubicin 2 weeks prior to the first dose of LED. All doses were given by 1-h infusion through a central vein. Toxicity was evaluated in 22 courses delivered to 17 patients. The MTD with this schedule was 30 mg/m2 per week x 3. The single patient treated at 37.5 mg/m2 weekly could not complete the entire course due to myelosuppression. At the dose of 30 mg/m2 per week, three of eight patients had grade > or = 3 leukopenia. Other toxicities included mild to moderate thrombocytopenia, nausea, vomiting, fever, alopecia, diarrhea, fatigue, stomatitis, and infection. At the dose of 30 mg/m2 per week, the total doxorubicin AUC and peak total doxorubicin concentrations in plasma were 8.75 +/- 8.80 microM h (mean +/- SD) and 3.07 +/- 1.45 microM, respectively, after LED administration. The total doxorubicin AUC and peak total doxorubicin concentrations in plasma were 3.92 +/- 2.47 microM h and 2.75 +/- 2.70 microM, respectively, after the infusion of standard-formulation doxorubicin. The total body clearance of doxorubicin was 18.42 +/- 11.23 l/h after the infusion of LED and 31.21 +/- 15.48 l/h after the infusion of standard-formulation doxorubicin. The mean elimination half-lives of doxorubicin were similar: 8.65 +/- 5.16 h for LED and 7.46 +/- 5.16 h for standard-formulation doxorubicin. Interpatient variability in pharmacokinetic parameters as demonstrated by the percentage of coefficients of variation was 33%-105%. There was no relationship between the percentage of WBC decrease or the duration of WBC suppression and the total doxorubicin or doxorubicinol AUC. There was no correlation between the duration of leukopenia and drug exposure as reflected by the AUC of liposome-associated doxorubicin. LED can be given in doses similar to those of standard-formulation doxorubicin and produces acute toxicities similar to those caused by standard doxorubicin.
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PMID:Phase I and pharmacokinetic trial of liposome-encapsulated doxorubicin. 826 69

Fourteen patients with diffuse malignant pleural mesothelioma (DMPM) were enrolled in a Phase II study to assess activity and toxicity of the systemic administration of recombinant (r)-alpha-interferon (IFN)-2b. The IFN schedule was: 3 x 10(6) IU i.m. days 1-4, 6 x 10(6) IU days 5-8, 10 x 10(6) IU days 9-12; then IFN was administered at 10 x 10(6) IU 3 days/week. If grades II-III toxicity occurred, IFN dose was reduced and drug continued at the previous dose level. All patients were evaluated by CT scan. Only one patient was not evaluable for response and toxicity because of inadequate follow-up. Of 13 evaluable patients, we observed 1 objective response, 6 stable disease, and 6 failures (3 progressive disease and 3 early interruptions due to subjective toxicity). The median time to progression was 19 weeks, and the median overall survival was 62 weeks. Toxicity was mild: of 13 patients evaluable for toxicity we observed fever (9 patients), flu-like syndrome (3 patients), fatigue (4 patients), anorexia (2 patients), myelosuppression (3 patients), and muscle pain (1 patient). The results of this study indicate only marginal activity of r-alpha-IFN in the treatment of DMPM.
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PMID:Recombinant interferon alpha-2b in the treatment of diffuse malignant pleural mesothelioma. 831 Oct 14

In December 1993, a 76-year-old Japanese male presented with general fatigue. Peripheral blood (PB) examination indicated marked leukocytosis (WBC count, 19.8 x 10(4)/microliter; leukemic blast differential, 89.5%). Leukemic blasts were positive for CD33, and negative for lymphoid antigens, with 2% of the blasts being positive for myeloperoxidase staining. On admission, chromosome analysis of leukemic cells in PB showed 45, X,-Y, t (9;22) [12/15]/46, XY, t (9;22) [3/15]. Southern blot analysis of the DNA from PB showed a rearrangement at the M-BCR region and germline configurations of both TCR beta and IgH chain genes. The patient was diagnosed as Philadelphia-positive chronic myelogenous leukemia (CML) in blast crisis. We commenced treatment with daunorubicin (DNR; 20 mg/day x 1 IV) and daily prednisolone (PSL; 60 mg/day PO). Leukemic blasts disappeared rapidly from PB, while the promyelocytes showed a transient increase, peaked 7 days after the start of therapy, and then disappeared. Myelocytes and metamyelocytes also showed transient increases. Without a period of severe myelosuppression, the patient reverted to the chronic phase of CML and karyotypic analysis of bone marrow cells showed 45, X,-Y, t (9;22) [33/35]/46, XY, [2/35]. Consolidation chemotherapy with DNR and BHAC was started, but the patient's condition deteriorated due to bacterial infection and he died of hepatic failure on March 1994. In this case, reversion to the chronic phase of CML in blast crisis may be accomplished by the cytodifferentiating effects of small-dose DNR and oral PSL to the leukemic blasts.
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PMID:[Reversion to chronic phase of chronic myelogenous leukemia in blast crisis with small-dose daunorubicin and oral prednisolone]. 858 71

LY188011 (Gemcitabine hydrochloride) is a new derivative of deoxycytidine. Phase I study was carried out by a cooperative study group. LY188011 was administered weekly for 3 consecutive weeks starting with an initial dose of 60 mg/m2 (1n) and then increasing the dosage to 1,000 mg/m2 (16.7n). Dose limiting factor was found to be myelosuppression (decreases of WBC, neutrophils and platelet), and MTD was considered to be 1,000 mg/m2. The nadir of WBC and platelet were observed after about 1-3 weeks. It took 1-2 weeks for their recovery. Other adverse reactions included fever, fatigue, anorexia, nausea/vomiting, anemia and transient elevations of GOT and GPT. However, those adverse reactions were mild. T1/2 rho of plasma concentration was about 19 min and the C5min was dependent on the dose. Anti-cancer effects were observed in one gastric cancer and two colon cancer patients. It is recommended that the dosing schedule for an early phase II study is 800 mg/m2 weekly for 3 weeks with 1 week of rest as one cycle, in multiple cycles.
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PMID:[LY188011 phase I study. Research Group of Gemcitabine (LY188011)]. 868 15

A multi-institutional cooperative group trial was undertaken by the Cancer and Leukemia Group B (CALGB) to evaluate the efficacy of the combination of cisplatin and intravenous etoposide for the treatment of metastatic or recurrent non-small cell lung cancer (NSCLC). The doses used were those previously determined to be the maximally tolerated dose of this drug combination. Forty patients were entered into the trial, 37 of whom were eligible for evaluation. Cisplatin (35 mg/M2/day for 3 days) and etoposide (200 mg/M2/day for 3 days) were administered every 28 days for a planned 6 cycles of therapy. Sixteen of 37 evaluable patients (43%) responded to therapy. Myelosuppression was the dominant toxicity, with 89% of the patients experiencing grade 4 neutropenia, and nearly half grade 3 or 4 thrombocytopenia. Median survival was 8.5 months, with 30% of the patients alive at 1 year and 10% alive at 2 years. Malaise, fatigue, and peripheral neuropathy were the other major toxicities. The combination of etoposide at the dose of 200 mg/M2/day for 3 days and cisplatin at 35 mg/M2/day for 3 days is a highly potent combination against metastatic non-small cell carcinoma.
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PMID:Etoposide (VP-16) and cisplatin at maximum tolerated dose in non-small cell lung carcinoma: a Cancer and Leukemia Group B study. 871 68


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